Graft-versus-Host Disease (GVHD)

Immunosuppression is the headline - Every allogeneic transplant patient gets GVHD prophylaxis, most commonly cyclosporine plus methotrexate for several months, with antibacterial, antiviral and antifungal prophylaxis layered on. Grade 2 or higher disease adds systemic methylprednisolone 2 mg/kg/day in divided doses, and chronic GVHD generally means 2 to 3 years of steroids, sometimes lifelong. Recurrent infection is a common cause of death here - full barrier technique for every line and block, and don't dismiss a fever.

Skin will not tolerate ordinary handling - Histologic damage ranges from minimal vacuolization to frank separation of dermis from epidermis, and severe acute GVHD produces bullous lesions mimicking toxic epidermal necrolysis. Lift, never drag. Use non-adhesive securement, pad every pressure point, and think hard before putting an adhesive grounding pad or a frequently cycling NIBP cuff over involved skin - an arterial line may be kinder for a long case.

Dry eyes, dry mouth - Ocular involvement carries a poor prognosis and usually presents as dry eye or keratoconjunctivitis sicca. Tape and lubricate the eyes before the drapes go on, because a dry cornea abrades immediately. Oral chronic GVHD presents as lichen planus, and mucositis with mucosal ulceration is common in acute disease - gentle laryngoscopy and a soft suction catheter, not a Yankauer dragged across the palate.

Airway in sclerodermatous change - Chronic GVHD has many features in common with systemic sclerosis (see the Systemic Sclerosis entry), so measure mouth opening, interincisor distance and neck extension at the bedside rather than trusting the chart. Oral lichen planus also carries a risk of squamous cell carcinoma that appears more aggressive in stem cell transplant patients, so a new oral lesion is worth pointing out, not stepping around.

Obstructive lung disease is the sleeper - GVHD is associated with bronchiolitis obliterans syndrome, obliterative bronchiolitis, organizing pneumonia, interstitial lung disease and pleuroparenchymal fibroelastosis, and bronchiectasis can follow. Get spirometry and a DLCO rather than relying on a report of exercise tolerance. Expect fixed obstruction, plan longer expiratory times, and watch the flow-volume loop and plateau pressure for auto-PEEP.

Gut GVHD means volume and electrolytes - Diarrhea is secretory and continues despite fasting, starts watery and can turn bloody, may require frequent transfusion, and makes fluid balance genuinely difficult. Malnutrition is common with deficiencies in zinc, magnesium, vitamin B12 and vitamin D. Send a magnesium with the basic panel and correct it before induction. An NPO order does not mean a quiet gut.

Liver involvement changes drug handling - Hepatic GVHD typically shows elevated bilirubin and alkaline phosphatase; coagulopathy and hyperammonemia are rare but occur in severe forms. Check an LFT panel and INR. With a rising bilirubin, titrate hepatically cleared agents to effect rather than to weight.

Every cellular blood product must be irradiated - Irradiation prevents transfusion-associated GVHD and leukoreduction reduces febrile nonhemolytic reactions, HLA alloimmunization and CMV transmission. Write it on the order. Thrombocytopenia is routine enough that liver biopsy is avoided for it, so get a platelet count before any neuraxial or deep block.

Steroid-refractory disease has its own drugs - Ruxolitinib, a JAK inhibitor, is used for steroid-refractory acute GVHD. Add-on agents include mycophenolate, sirolimus, etanercept, pentostatin, monoclonal antibodies, alpha-1-antitrypsin and extracorporeal photopheresis. Reconcile the list before you dose anything - cyclosporine and sirolimus interact widely, and a patient on photopheresis has a central line that belongs to the transplant team.

Graft-versus-host disease (GVHD) occurs when immunocompetent donor T lymphocytes in an allogeneic graft recognize recipient MHC/HLA as foreign and attack it - a type IV cytotoxic T-cell reaction driven mainly by donor CD8+ cells. It is a common complication of allogeneic hematopoietic stem cell transplant and is classically split at 100 days into acute and chronic.

Acute GVHD strikes skin (70%), gastrointestinal tract (74%) and liver (44%), and occurs in up to 50% of transplants from an HLA-matched sibling, more with mismatched donors. Chronic GVHD shares many features with collagen vascular disorders and systemic sclerosis. More than 10% of transplant patients die of GVHD. Perioperatively you inherit a patient who is fragile in the skin, dry in every mucosa, obstructed in the lung and profoundly immunosuppressed.